Figure 7.

Results of sensitivity analysis demonstrating failure of pacemaker function (AP firing ceased) in cell models with square lattice positions of CRUs, but not with uniformly random CRU distribution at lower, albeit physiological, I CaL densities. (A) Bridging experimentally measured ICaL densities (green circles) and our model parameter gCaL describing maximum ICaL conductance (magenta). The data points for ICaL experimental data were replotted from Monfredi et al. (2018). Magenta band shows range of gCaL in our sensitivity analysis. (B) Results of sensitivity analyses for cell models with uniformly random CRU distribution (red) and square lattice distribution (blue). Data points are average CLs evaluated between 5 and 16.5 s after simulation onset. Red shade square shows the gCaL margin where square lattice models failed, but uniformly random model continued generating spontaneous APs. (C) An example of AP firing failure in a square lattice model, but rhythmic AP firing in uniformly random model when in both cases gCaL reduced to 70% of its basal value. See original simulation data in Fig. S2.

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